JP2009526828A - Virus killing material - Google Patents

Abstract

The present invention is a compound of general formula M _n X _y for use in reducing and / or preventing viral transmission, wherein M is (i) calcium (Ca), aluminum (Al) A metal selected from the group consisting of zinc (Zn), nickel (Ni), tungsten (W) or copper (Cu); or (ii) consisting of silicon (Si), boron (B), or carbon (C) A nonmetal selected from the group; n is equal to 1, 2, or 3 and X is selected from the group consisting of (iii) oxygen (O), nitrogen (N), or carbon (C) Nonmetal; or (iv) phosphate (PO ₄ ³⁻ ), hydrogen phosphate (HPO ₄ ²⁻ ), dihydrogen phosphate (H ₂ PO ₄ ⁻ ), carbonate (CO ₃ ), silicate (SiO ₄ ²⁻ ) , sulfate (SO ₄ ^2-), nitrate (NO ₃ ^{-) -} in selected from the group consisting of anions, nitrite (NO ₂₎ Providing for the use of compound nanoparticles wherein y is equal to 0, 1, 2, 3, or 4. A protective clothing article or filter is provided in which fibers are coated with the nanoparticles for use in reducing and / or preventing viral transmission.

Description

  The present invention relates to the use of metal and / or metal compound nanoparticles in the prevention of viral infection.

  Airborne viral infections are generally caused by inhalation of water droplets containing viral particles. Larger droplets containing the virus accumulate in the nose while smaller droplets or nanoparticles are carried into the human respiratory tract or alveoli. The SARS virus, as shown in Figure 1, is magnified by droplets approximately 100-500 nm in size produced by coughing and sneezing, but other infection routes, such as facial contamination, may also be involved. (Donnelly et al. Lancet, 361, 1761-1777, (2003) (non-patent document 1)). Thus, from a filtration point of view, nanoscale viruses and particles can theoretically penetrate normal facial mask gaps. The diameter of ultrafine artificial or natural fiber filaments in the current world is approximately 7 micrometers. A standard facial mask as shown in FIG. 2 has a gap of approximately> 20 to 10 μm throughout the fiber mat.

Therefore, face masks using traditional filter cloth materials are unsuitable for stopping nanoscale viruses. The gap between the fibers of the facial mask is on average 10-30 μm (10,000-30,000 nm). Masks with smaller fiber gaps are thought to cause dyspnea. Other nanoscale airborne viruses and particles such as smoke and ultrafine dust can enter the human lung and then enter the blood system through the respiratory membrane. The health impact is primarily related to the submicron sized fraction of particles (ie, aerodynamic diameter, d _p , less than 1 μm). The danger from smoke particles is the fraction d _p <100 nm, and such small particles are produced in large quantities during the combustion process.

  Particles smaller than 100 nm are nanomaterials ranging in size, including the size of human viruses such as avian influenza and HIV. Global concerns about influenza (ie, the consequences of SARS and H5N1 virus infections) and AIDS are well-recognized problems in the modern world today, but no solution has been available to help prevent the spread of viral disease It is lacking. However, nanomaterials may provide a vital solution for humans to control these diseases. Solutions are urgently needed to address these infectious diseases.

  Nanoparticles can be electron microscopes such as transmission or scanning electron microscopes (TEM or SEM), atomic force microscopes (AFM), X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (XRD), and Fourier It can be characterized by transform infrared spectroscopy (FTIR).

  Nanoparticles find use in pharmaceutical formulations to improve the solubility and / or biological activity of drug substances. In addition to pharmaceutical or academic research purposes, nanoparticles are also used for medical purposes. For example, silver nanoparticles have been used to kill bacteria (Furno et al J. Antimicrob Chemother, 54 (6), 1019-24 (2004) (non-patent document 2)).

  Other studies have described the use of nanometric catalysts prepared with metals such as silver, titanium dioxide, zinc oxide, and carbon (Fang et al Virologica Sinica, 20, 70-74 (2005)) Reference 3)). Such a catalyst is a supported nanometer-sized metal catalytic crystal particle composition in which the exposed surface of the nanometer-size catalyst particles comprises predominantly (111) type crystal planes. Such catalysts include dissociative adsorption of hydrogen, surface reactions, and recombination / desorption, various hydrogenations, and methanation, carbonylation, hydroformylation, reductive alkylation, amination, hydrosilation, ammonia synthesis, oil or It has been used to promote related reactions such as fat hardening and the like. However, there is no suggestion that the metal or metal oxide nanoparticles themselves can have any virucidal properties.

Other studies in the field of virology have investigated the use of materials such as bentonite, a colloidal clay material. Bentonite nanoparticles have been prepared and reported to have virucidal activity. However, due to the complex nature of this material, it is not clear whether the mechanism of action is related to particle size or to the inherent properties of the material ( http : //www.eswiconference.org- 2005).

Recently, there is a report ( www.nanoscale.com ) that the use of nanoparticulate silver is effective as a drug to prevent virus replication. However, the data does not suggest any virucidal efficacy of the particles used on the physicochemical characteristics of the material itself (Elechiguerra et al J. Nanobiotechnology 3 (6) (2005)). . However, the use of silver is not 100% completely effective and has associated cost and toxicity issues.

  The impact of SARS, avian influenza, and human influenza virus outbreaks shows how the current defense repertoire is limited to viral infections. Accordingly, there is a need for improved means for preventing the transmission of viral particles.

Donnelly et al. Lancet, 361, 1761-1777, (2003) Furno et al J. Antimicrob Chemother, 54 (6), 1019-24 (2004) Fang et al Virologica Sinica, 20, 70-74 (2005) Elechiguerra et al J. Nanobiotechnology 3 (6) (2005)

According to a first aspect of the present invention, there is provided a compound of general formula M _n X _y for reducing and / or preventing viral transmission, wherein M is (i) calcium (Ca), aluminum (Al ), A metal selected from the group consisting of zinc (Zn), nickel (Ni), tungsten (W) or copper (Cu);
Or (ii) a non-metal selected from the group consisting of silicon (Si), boron (B), or carbon (C);
n is equal to 1, 2, or 3,
And X is (iii) a non-metal selected from the group consisting of oxygen (O), nitrogen (N), or carbon (C);
Or (iv) phosphate (PO ₄ ³⁻ ), hydrogen phosphate (HPO ₄ ²⁻ ), dihydrogen phosphate (H ₂ PO ₄ ⁻ ), carbonate (CO ₃ ), silicate (SiO ₄ ²⁻ ), sulfate ( An anion selected from the group consisting of SO ₄ ²⁻ ), nitrate (NO ₃ ⁻ ), nitrite (NO ₂ ⁻ );
y equals 0, 1, 2, 3, or 4;
The use of compound nanoparticles is provided.

  Nanoparticle means a particle having a dimension of nanometer, and the nanoparticle may have a dimension of approximately several nanometers to several hundred nanometers, for example. The nanoparticles may be similar in size to any given one or more viruses or smaller than any given one or more viruses.

  Nanoparticles for use according to the present invention may have an average particle size of up to about 100 nm, up to about 200 nm, up to about 300 nm, or up to about 500 nm. Preferred average particle sizes may be in the range of about 1 nm to about 90 nm, preferably about 5 nm to about 75 nm or about 20 nm to about 50 nm. A particularly preferred average particle size range is from about 20 nm to about 50 nm.

Preferred specific surface area of the particles, 150 meters ² / g to about 1450 m ² / g, preferably, may be in the range of 200 meters ² / g to about 700 meters ² / g, the preferred values, 150m ² / g, 640m ² / g, 700m ² / g may be included. The voids in the particles may be about 0.1 to about 0.8 ml / g, suitably 0.2 to about 0.7 ml / g, preferably about 0.6 ml / g.

  The nanoparticles are usually preferably in the form of a dry powder, but can be in the form of nanotubes as well as liquids, sol-gels, or polymers. The particles may be agglomerated or freely associated.

Nanoparticles may contain a single element M in the general formula M _n X _{y where} y is equal to 0 and thus X is not present, or the nanoparticles have a value of y of 1, 2, or 3 And x may vary accordingly with respect to the value of y consistent with the respective valence of elements M and X present in the formula, it may include compounds as defined above.

  Alternatively, single element nanoparticles where y is equal to 0 are the group consisting of silicon (Si), boron (B), phosphorus (P), arsenic (As), sulfur (S), or gallium (Ga) May be doped with one or more elements selected from; aluminum (Al), manganese (Mn), magnesium (Mg), nickel (Ni), tin (Sn), copper (Cu), titanium ( It may be alloyed with one or more elements selected from the group consisting of Ti), tungsten (W), silver (Ag), or iron (Fe).

  For example, mixed nanoparticles may be composed of different elements such as: CP-Ag-Zn, CP-Cu-S, CP-Cu-Ni-S, C-Si-Ag-Zn, C -Si-Cu-S, C-Si-Cu-Ni, C-Cu-Zn-W, C-Cu-Zn-Ag, C-Cu-Zn-W-Ag, CW-Ti-B, CW-Ti -N, C-Ti-N, Si-N, Ti-N, Al-N, BN, Al-B.

Nanoparticles may also further comprise at least one of the following _{oxides: TiO 2, Cu 2 O,} CuO, ZnO, NiO, Al 2 O 3, FeO, Fe 2 O 3, Fe 3 O 4 , CoO, Co ₃ O ₄ , or Si ₂ O ₃ , or a combination thereof.

Preferred compounds of the general formula M _n X _y are oxides, carbonates, silicates, carbides, may also be a nitride, and / or phosphates.

For example, aluminum oxide (Al ₂ O ₃ ), silicon dioxide (SiO ₂ ), zinc oxide (ZnO), aluminum phosphate (ie, aluminum phosphate (AlPO ₄ ), aluminum hydrogen phosphate (A1 ₂ (HPO ₄ ) ₃ ) ), Aluminum dihydrogen phosphate (Al (H ₂ PO ₄ ) ₃ )), calcium oxide (CaO), calcium carbonate (CaCO ₃ ), calcium silicate (CaSiO ₄ ), calcium phosphate (ie, calcium phosphate (Ca ₃ (PO _{3 4} ) ₂ ), calcium hydrogen phosphate (CaHPO ₄ ), or calcium dihydrogen phosphate (Ca (H ₂ PO ₄ ))), silicon nitride (Si ₃ N ₄ ), silicon carbide (SiC), boron nitride (BN ), Tungsten carbide (WC), titanium carbide (TiC), or titanium carbonitride (TiC _0.5 N _0.5 ).

  Nanoparticles may also be prepared as layered (core / shell) particles comprising an inner core and an outer shell.

Other aspects of the present invention may include the use of a mixed composition of nanoparticles. Thus, for example, a mixed composition may comprise one or more compounds of the general formula M _n X _y as above (ie, at least two such compounds) or boron (B), carbon (C), aluminum (Al), silicon (Si), phosphorus (P), calcium (Ca), titanium (Ti), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), silver (Ag), zinc (Zn), copper (Cu), sulfur (S), nickel (Ni), gold (Au), zirconium (Zr), ytterbium (Yb), zirconium (Zr), or an oxide thereof or An additional element selected from the group consisting of combinations may further be included. Preferred oxides may include, for example, titanium dioxide (TiO ₂ ) or zirconium oxide (ZrO ₂ ).

The mixed composition of nanoparticles may be copper (Cu), copper (II) oxide (CuO), and / or copper (I) oxide (Cu ₂ O). The nanoparticle is a compound of the general formula M _n X _y as defined according to the first aspect and aluminum (Al), silicon (Si), zinc (Zn), or nickel (Ni), or combinations thereof One or more mixed compositions may be included. In such embodiments, the nanoparticles may include:
(I) Aluminum (Al) and aluminum oxide (Al ₂ O ₃ ),
(Ii) silicon (Si) and silicon dioxide (SiO ₂ ),
(Iii) silicon (Si) and silicon carbide (SiC),
(Iv) zinc (Zn) and zinc oxide (ZnO), or (v) nickel (Ni) and nickel (II) oxide (NiO)
Or a combination.

The nanoparticles may further comprise one or more of titanium dioxide (TiO ₂ ), zinc oxide (ZnO), and titanium dioxide (TiO ₂ ).

  Mixtures of more than one of the above may also be prepared and used according to the present invention. Mixed nanomaterial compositions may be produced by any suitable method, such as, for example, tumble-mixing, co-deposition, mechanical alloying, and the like.

  Thus, the use according to the invention also extends to mixed oxides, non-stoichiometric particles.

  Nanoparticle synthesis can be considered to include two main areas: gas phase synthesis and sol-gel processing. Nanoparticles may be produced by evaporation and condensation (nucleation and growth) in an inert gas environment below atmospheric values. Various aerosol processing techniques may be used to improve the production yield of the nanoparticles. These include synthesis by combustion flame, plasma, laser ablation, chemical vapor condensation, spray pyrolysis, electrospray, and plasma spray.

  Sol-gel processing is a wet chemical synthesis approach that can be used to produce nanoparticles by gelation, precipitation, and hydrothermal treatment. The size distribution of the semiconductor, metal, and metal oxide nanoparticles can be manipulated by either dopant introduction or thermal treatment. Better size and stability control of quantum confined semiconductor nanoparticles can be achieved through the use of polymer matrix structures based on reverse micelles, block copolymers or polymer blends, porous glass, and ex situ particle capping techniques.

  Other nanoparticle synthesis techniques include sonochemical processing, cavitation processing (eg, using a piston gap homogenizer), microemulsion processing, and high energy ball milling. In sonochemistry, the acoustic cavitation process can produce a transient, localized hot zone with extremely high temperature gradients and pressures. Such sudden changes in temperature and pressure aid in the destruction of sonochemical precursors (eg, organometallic solutions) and the formation of nanoparticles.

  In hydrodynamic cavitation, nanoparticles are generated through the creation and release of bubbles inside the sol-gel solution. The sol-gel solution is mixed by rapid pressurization in a supercritical drying chamber and exposure to cavitation disturbances and high temperature heating. The ejected hydrodynamic bubbles lead to nanoparticle nucleation, growth, and quenching. By adjusting the pressure and solution retention time in the cavitation chamber, the particle size can be controlled.

Microemulsions can be used to synthesize metal nanoparticles, semiconductor nanoparticles, silica nanoparticles, barium sulfate nanoparticles, magnetic nanoparticles, and superconducting nanoparticles. Controlling very low interfacial tension (approximately 10 ^-3 mN / m) through the addition of cosurfactants (eg medium chain length alcohols) produces these microemulsions spontaneously without the need for significant mechanical agitation Is done. This technology is useful for large-scale production of nanoparticles using relatively simple and inexpensive hardware. High energy ball milling has been used to produce magnetic nanoparticles, catalytic nanoparticles, and structural nanoparticles.

  It is often important to achieve controlled production of monodisperse nanoparticles with very little size variation so that size selection by centrifugation or mobility classification is not necessary. Among all the synthesis techniques discussed above, gas phase synthesis is effective not only by using a combination of strict control of nucleation-condensation growth and avoiding solidification by diffusion and perturbation, but also by the effectiveness of nanoparticles. It is one of the best techniques for size monodispersity that is also typically achieved by successful recovery and subsequent handling thereof. By recovering the nanoparticles in the liquid dispersion, the stability of the recovered nanoparticle powder against agglomeration, sintering, and composition change can be ensured. Surfactant molecules have been used to stabilize the liquid dispersion of metal nanoparticles. Alternatively, inert silica encapsulation of nanoparticles by gas phase reactions and by oxidation in colloidal solutions has been shown to be effective for metal nanoparticles.

  Approaches have been developed for the production of monodisperse nanoparticles that do not require the use of a size classification procedure. Monodispersed gold colloidal nanoparticles with a diameter of about 1 nm can be prepared by reduction of metal salts by UV irradiation in the presence of dendrimers. Poly (amidoamine) dendrimers with higher generation surface amino groups have a spherical 3D structure that can have an effective protective action for the formation of gold nanoparticles.

  One production method that is suitable for the production of these materials is the Tesima® process (International Publication Nos. 01/78471 and 01/7841), in which plasma is generated in an inert gas envelope using high temperature DC plasma. 58625). Materials (either pre-produced feedstocks or mixed feedstocks) or liquids can be placed in the plasma and they can be evaporated very rapidly. The resulting vapor then leaves the plasma where it is subsequently cooled with a large amount of cooling gas. These gases can either be inert (such as argon or helium) or air, or to develop the required chemistry / morphology / size Of trace components. Thereafter, rapid cooling (greater than 100,000 degrees per second) freezes the particles for subsequent cooling and recovery using a combination of techniques that can include solid or fabric filters, cyclones, and liquid systems. The material can also be recovered directly either in a container or in various liquids under inert gas.

  In certain embodiments of the invention, the generation of a plasma within an inert gas envelope and the insertion of substances and / or liquids containing one or more elements or compounds of one or more elements, or mixtures thereof into the plasma, Nanoparticles are prepared by a process that includes gas cooling of the resulting vapor upon exiting the plasma.

  Reduction and / or prevention of viral transmission may be defined as a reduction in viral titer of at least 90% after administration of a nanoparticulate composition as defined herein to a viral preparation. Preferably, the reduction in virus titer is at least 93%, 94%, or 95%, most preferably 98%, 99%, or 100%. Reduction and / or prevention of viral transmission is evidenced by virus inactivation upon contact with the nanoparticles.

  A reduction in viral titer of 70% or less is not an effective reduction enough to avoid infection. The present invention provides a means for reducing virus titer so that infection is prevented or avoided to a significant extent.

  Virus titer is a quantification of the number of virus particles in a given sample. It may be done by using a hemagglutination assay (HA). The virus family has surface or envelope proteins that can aggregate animal erythrocytes (RBC) and bind to N-acetylneuraminic acid residues on the cell surface of RBCs. RBCs form a kind of lattice that can be quantified after virus binding.

  The HA procedure is a simple, simple and rapid method and can be applied to large samples. Detailed conditions depend on the type of virus. Some viruses bind to RBC only at certain pH values, while others bind at a certain ionic strength. However, these are well known to those skilled in the art and can be easily identified depending on the virus in question. Virus dilution is applied to the RBC dilution for a suitable period under appropriate conditions. Thereafter, the lattice formation is measured and the titer is calculated.

  The present invention provides a means for reducing the viral titer of a virus, preferably the virus is influenza, measles, coronavirus, mumps, marburg, ebola, rubella, rhinovirus, poliovirus, hepatitis A Smallpox, chickenpox, severe acute respiratory syndrome virus or SARS virus (also called SARS coronavirus), human immunodeficiency virus (HIV), and simian immunodeficiency virus (SIV), rotavirus, norwalk virus, And a related non-human animal immunodeficiency retrovirus such as adenovirus. Norwalk virus includes its feline calicivirus. Influenza viruses include both human and avian viruses.

  Accordingly, the present invention also provides a composition comprising nanoparticles as described above for use as an antiviral agent. Nanoparticles are not only suitable carriers, coating agents, or solvents such as water, methanol, ethanol, acetone, water-soluble polymer adhesives such as polyvinyl acetate (PVA), epoxy resins, polyesters, but also crosslinking agents, charged It may be suitably formulated into an inhibitor. A solution of biological material such as phosphate buffered saline (PBS) or simulated biological fluid (SBF) may also be used.

  The concentration of nanoparticles in the solution may range from 0.001% (wt) to about 20% (wt).

In one embodiment of this aspect of the invention, a compound of the general formula M _n X _y for reducing and / or preventing viral transmission, wherein M is (i) calcium (Ca), aluminum ( A metal selected from the group consisting of Al), zinc (Zn), or copper (Cu);
Or (ii) a non-metal selected from the group consisting of silicon (Si) or carbon (C);
n is equal to 1 or 2,
And X is (iii) a non-metal selected from the group consisting of oxygen (O), nitrogen (N), or carbon (C);
Or (iv) phosphate (PO ₄ ³⁻ ), hydrogen phosphate (HPO ₄ ²⁻ ), dihydrogen phosphate (H ₂ PO ₄ ⁻ ), carbonate (CO ₃ ⁻ ), silicate (SiO ₄ ²⁻ ), sulfate An anion selected from the group consisting of (SO ₄ ²⁻ ), nitrate (NO ₃ ⁻ ), nitrite (NO ₂ ⁻ );
y equals 0, 1, 2, or 3;
Use of nanoparticles with an average particle size of up to 100 nm of the compound is provided.

  To reduce and / or prevent viral transmission, prevent viral transmission from a first location to a second location, eg, from an external space to an internal lumen, or through a barrier material. In addition, prevention of viral infection by the subject virus is included. The subject may be a human or non-human animal, preferably a non-human mammal. Thus, the present invention may find application in applications in the fields of human medicine and veterinary medicine as well as in the field of infection control in non-medical contexts, such as prophylactics against viral transmission.

  According to a second aspect of the present invention there is provided a method for the reduction and / or prevention of viral transmission comprising the step of applying a nanoparticulate composition as defined above to a protective clothing article.

  The nanoparticles used in accordance with this aspect of the invention may be formulated into a composition as described above.

  The coating process may be by any generally suitable means such as spray coating, electrospray coating, dipping, plasma coating, and the like.

  Such protective clothing articles may be prepared from any suitable fiber or fabric, such as natural or artificial fibers. Natural fibers include cotton, wool, cellulose (including paper materials), silk, wool, jute, hemp, sisal, flax, wood and bamboo. Artificial fibers include polyester, rayon, nylon, Kevlar (registered trademark), lyocell (Tencel (registered trademark)), polyethylene, polypropylene, polyimide, polymethylmethacrylate, poly (carboxylate phenoxy) phosphazene PCPP, fiber glass (glass) ), Ceramic, metal and carbon. The clothing article may be selected from the group consisting of a facial mask (surgical mask, respirator mask), hat, hood, trousers, shirt, gloves, skirt, boiler suit, surgical gown (scrub), and the like. Such clothing can find particular use in hospitals where control of infection is important.

  According to a third aspect of the present invention there is provided a method for the reduction and / or prevention of viral transmission comprising the step of applying a composition of nanoparticles as defined above to a filter. The application of the nanoparticle composition may be as described in connection with the second aspect of the invention.

  The filter may be prepared from any suitable natural or artificial material as described above in connection with the second aspect of the invention.

  The filter may be an air filter. An air filter is a device that removes contaminants, often solid particles, from the air. Air filters are often used in any other situation where air quality is important, such as in submersible air compressors, ventilation systems, and air conditioning equipment. Air filters include devices that filter not only instruments or chambers for handling viral material, but also air in enclosed spaces such as buildings or rooms. Thus, other articles that perform protective functions such as curtains or screens may also be considered air filters. Thus, an air filter according to this aspect of the invention may also be prepared according to the second aspect of the invention.

  The air filter may be composed of paper, foam, cotton filter, or spun fiberglass filter elements. Alternatively, the air filter may use fibers or elements having an electrostatic charge. There are four main types: paper, foam, chemically synthesized, and cotton mechanical air filters.

  An example of a pleated paper air filter designed for use in ducts with home heating, ventilation, and air conditioning (HVAC) systems is the 3M “filterlet” product.

  Polyester fibers can be used to form webs used for air filtration. Polyester can be blended with cotton or other fibers to produce a wide range of performance characteristics. In some cases, polypropylene may be used. Very small synthetic fibers known as microfibers may be used in many types of HEPA (High Efficiency Particulate Air Filter) filters. The high performance air filter may use a layer of cotton gauze that has been processed with oils and fats.

  Alternatively, the liquid may be filtered using a filter. Such a filter may be composed of any suitable fiber as described above. Fluids for medical use, such as potable liquids for consumption by humans or animals, water for normal household use, plasma or saline solution, for injection using filters used to filter liquids Pharmaceutical formulations or other biological fluids that may come into contact with the patient may be filtered.

  According to a fourth aspect of the present invention there is provided a protective clothing article composed of fibers coated with a nanoparticle composition as described above. The protective clothing article may preferably be a facial mask. Such a mask may cover the entire face of the user or part thereof, preferably the outer region of the wearer's nose and / or mouth.

  According to a fifth aspect of the present invention, there is provided a filter composed of fibers coated with a nanoparticle composition as described above. Suitably the filter may be an air filter.

  It should be noted that in aspects of the invention relating to protective apparel or filters, the protective apparel or filter can be made from mixed fibers from any source as described above.

  In a preferred embodiment of the present invention there is provided a face mask or filter composed of a fibrous material that is coated with a nanoparticle composition as defined herein.

The present invention also provides the use of mixed nanoparticles of zinc oxide (ZnO) and titanium dioxide (TiO ₂ ) to reduce and / or prevent viral transmission. Such mixed nanoparticles of the present invention may also be used in a method as described above, or in a filter as described above, or in a protective clothing article as described above.

  Preferred features for the second and subsequent aspects of the invention are the same as for the first aspect with the necessary modifications.

  The invention will now be further described with reference to the following examples and figures, which are provided for purposes of illustration only and should not be considered as limiting the invention. Reference is made in the examples to many figures.

Example 1: Preliminary study on antiviral properties of nanomaterials Over 60 different through biological assessment using HA procedure to quantify the amount of influenza virus, hemagglutinin (HA) antigen present in samples The material was screened.

material:
96U well or V-bottom microtiter plate Turkey red blood cell (TRBC)
Phosphate buffered saline (PBS)
50ml pipette disposable pipette tips

Method
1. Add 50 ml PBS to all wells in rows 2-12 of microtiter plate.
2. Add PBS to the first well, the amount depends on the required sample diluent.
3. Virus sample treatment: Add an aqueous solution or suspension containing about 0.1 to 1% nanoparticles or test material.
4. Add sample in appropriate volume to first row of wells (each sample and dilution range should be done in duplicate).
5. Dilute the sample across the plate in rows 1-11.
6. Make 0.5% TRBC solution in PBS.
7. Add 50 ml of 0.5% TRBC to all wells used and row 12 (RBC control).
8. Place plate on mixer platform for 30 seconds to promote uniform distribution of TRBC.
9. Leave the plate at room temperature for 30 minutes to fix.
10. Read the plate.
11. Plates should be read and graded as follows:

Negative results A pellet should form at the bottom of the well. If the plate is tilted to 45 °, the pellet should form stripes as the TRBC slowly moves down. This indicates that there is not enough virus viron to crosslink TRBC.

Positive result
Positive results are seen when TRBC aggregates and forms a matrix that diffuses throughout the well. This indicates that virus viron is present in an amount sufficient to crosslink TRBC (two test plates as shown in FIG. 4).

  If the virus titer is relatively high in the context of TRBC, disrupted hemagglutination can occur. This can appear on the pellet at the bottom of the well, but with a tilted plate it remains in place. If this happens, it is advisable to repeat the assay using a lower titer.

  The endpoint of the assay is defined as the lowest virus reduction (highest dilution) that still causes hemagglutination.

  Viral titers are recorded as hemagglutination units (HAV) and directly correlated with dilution at the end of the well.

Example 2: Hemagglutination assay using different natural and man-made materials To test this, the HA assay was used to initiate screening of viral responses against natural and man-made nanomaterials. The goal was to identify and classify nanomaterials that are most effective at inactivating viruses to protect against influenza and SARS. Several natural and man-made nanomaterials have been identified that possess special properties that neutralize or inactivate standard A / B influenza viruses.

  The tests used neat virus B / GD AL444, VCI / 256, and other influenza viruses to test different materials.

  Neat HA (NHA): 1/512 at room temperature, 1/256 to 1/512 at 37 ° C .; virus response to material is shown as% reduction in virus titer (virus-material titration-VTMHA). During the test, after the virus solution was mixed with the material, the mixture was left at room temperature 20 ° C. or in an incubator for 30 minutes at 37 ° C. More than 20 elemental nanoparticles and their compounds have been tested so far, and some of them have gained virucidal rates of over 90%. Table 1 shows that 12 of over 60 samples were HA tested.

  One of the results of the preliminary B / GD virus response test was a reduction in viral load in the HA assay by adding a small percentage of nanomaterial. These results indicate a decrease in viral activity. Some of the nanomaterials could completely neutralize / inactivate the virus' ability to bind to red blood cells.

  FIG. 5 and FIG. 6 show the test results of the virus level change (%) by adding nanoparticles of different metals, metal oxides and their compounds related to Tables 1 and 2.

^＊ナノ材料によって産生されたウイルス力価の減少が70％未満である場合、ナノ材料は抗ウイルス効果を有さないと見なされた。 (Table 1) HA test results using nanomaterials as antiviral agents

^{* A} nanomaterial was considered to have no antiviral effect if the reduction in viral titer produced by the nanomaterial was less than 70%.

Type A: nano Al, nano Al ₂ O ₃ , and related compounds.
Type B: Nano Si, nano SiO _2, and related compounds.
Type C: nano SiC and related compounds.
Type D: nano Zn, ZnO, and related compounds.
Type E: nano Cu, CuO, CuO ₂ and related compounds.
Type F: Nano Ag and related compounds.
Type G: nano Ni and NiO ₂ and related compounds.
H: Nano bentonite particles.
I: Nano TiO ₂ related material.

(Table 2) HA test results using nanomaterials as antiviral agents (antiviral nanocomposites)

Analysis of HA assay results In order to find new materials for face masks and filters that could interact with influenza / SARS virus, we set out to screen for viral responses to nanomaterials using biological assays. Nanomaterials have been identified that possess special properties that neutralize or inactivate standard influenza viruses. Short-term testing has focused on screening potential nanomaterials and classifying the most effective materials to be used to inactivate viruses in facial mask and filter applications.

Without being bound by theory, small size and highly activated nanoparticles (such as SiO ₂ ), which can be either hydrophilic or hydrophobic (or both at the same time), nanometers that are the same size as viruses The current assumption is that TiO ₂ particles, metal particles (Au, Cu), and ceramic particles (SiC, Al ₂ O ₃ ) may be taken up by viruses.

  The strong surface functionality of nanomaterials may mimic the interaction of animal cells with viruses.

  This study explored the use of nanoparticles for use as virucidal agents, and identified the most effective nanoparticles as targets for developing coating materials specifically to absorb viruses. Low cost face masks coated with antiviral nanoparticles may stop the virus by attraction or contact, but are believed to provide significant subsequent virus inactivation. It has been observed that nanomaterials smaller than 100 nm are more effective in terms of antiviral activity. One fiber coated with antiviral nanoparticles observed by SEM is shown in FIG. A particle is a mixture of different nanomaterials and compounds. Nanomaterials according to the present invention can be applied to enclosed ventilation fabrics for public buildings, hospitals, and modes of transport such as vehicles, cars, trains, ships, and airplanes. Nanoparticles will also find use in medical applications such as filtering materials, ie, filtering biological fluids such as plasma, blood, milk, semen, etc. to inactivate viruses.

  In order to produce products with antiviral properties, antiviral nanoparticles may be coated on the surface of different products such as cloth and fixtures, paint / coating agents, book covers, computer keyboards and the like. Such products will provide hospitals, children, patients and the elderly with a low cost and virus free environment. Further uses include air ventilation systems for enclosed environments such as passenger aircraft, large buses, and large vehicles to prevent the entry and exit of nanoparticles and airborne influenza viruses and other infectious viruses. May be.

  One of the preliminary B / GD virus reactions to nanomaterials shows how to reduce the viral load in the HA assay by adding a small percentage of nanomaterials, and how to prevent virus transmission It has been shown that nanomaterials can be used. Some of the materials can completely neutralize / inactivate the ability of the virus to bind to red blood cells in the HA assay.

  Preliminary results of B / GD virus screening demonstrated a reduction in viral load in the HA assay by adding a small percentage (<1%) of nanomaterials or compounds.

Inorganic nanocompounds such as calcium phosphate that can be coated with metals and metal oxides, as well as ceramics such as SiC, alumina, nano Ag, Cu, Zn, Al, nanoscale CuO, Cu ₂ O, Al ₂ O ₃ , TiO ₂ , Test results of virus level changes (in percentage) with the addition of different nanoparticles such as metal and metal oxides such as nano ZnO. CP-Ag-Zn, CP-Cu-S, CP-Cu-Ni-S, C-Si-Ag-Zn, C-Si-Cu-S, C-Si as shown in Table 3 and Table 4 Composite nanoclusters of combinations of inorganic and mineral compounds coated with metals and metal oxides, such as nanocompounds containing mixed elements such as -Cu-Ni, are also part of the present invention.

  Current results have identified a set of nanomaterials with improved antiviral activity superior to other nanomaterials such as silver. This academic study produces nanoscale clusters (eg nanoparticle materials available from manufacturers such as QinetiQ Nanomaterials Limited), inorganic / organic nanoparticle combinations, mineral compounds, and metals and metals The benefits of using multiple of each nanomaterial coated with oxide are also shown.

This result shows that there are many kinds of compound materials: nano Ag (poor), TiO ₂ (poor), ZnO (good), alumina (good), and Al-phosphate, etc., all exhibiting a virucidal rate exceeding 90% Al related compounds, Cu and Cu related oxides and compounds, Ca ²⁺ related compounds such as Ca phosphate, Ca silicate, and Ca carbonate, Si related compounds such as SiO ₂ and SiC, and P such as Al phosphate In addition to related compounds, as well as activated carbon, it shows that 20 nanoparticles have been tested.

  For example, using a cluster of compounds to deal with different influenza viruses and SARS viruses, multi-element multi-oxide compounds and mixtures according to the present invention can be used to address multiple viral transmissions and potential viral contamination. It may be used.

(Table 3) Materials for use in antiviral applications

(Table 4) Material combinations for antiviral applications

Example 3: Preliminary study on the virucidal efficacy of nanoparticles against avian H5N1 influenza NIBRG-14 virus This example examines the virucidal efficacy of test nanomaterials against avian H5N1 influenza NIBRG-14 virus using MDCK cells Because of the results of the study. In the test, the avian H5N1 influenza NIBRG-14 virus was used to test different materials.

The amount of virus tested in the “reaction mixture” was 10 ^6.5 TCID ₅₀ / ml (Tissue Culture Infective Unit). The effect of nanomaterials on the virus is shown as a reduction in virus titer (% and Log ₁₀ TCID ₅₀ / ml). Virus was diluted in distilled water (1:10 dilution from a stock of 10 ^7.5 TCID ₅₀ / ml virus grown in eggs). Thereafter, virus (200 ul) was added to the nanomaterial to form a “reaction mixture”. Lightly vortex (mix for 5 seconds) the reaction mixture (nanomaterial and virus solution) at room temperature (20 ° C), then shake on a plate shaker to ensure constant contact with the nanomaterial virus particles Incubated for an additional 30 minutes at room temperature.

Eight test nanomaterials were selected for analysis of virucidal action from the most promising materials previously tested in the HA assay. At the end of the 30 minute incubation, the reaction mixture was centrifuged to separate the nanomaterial from the virus and then added to the cell maintenance medium (in a 1:10 ratio) in preparation for infecting MDCK cells. The virus was then quantified by making serial dilutions of the reaction mixture on MDCK cells to generate an “infection” titer (Log ₁₀ TCID ₅₀ / ml). To test for assay performance, a “negative control” (no nanomaterial mixed with virus) and a “positive control” of citric acid (solution at a pH of approximately 3.5) were used.

Results These results show a decrease in viral activity from virucidal experiments. Some of the test nanomaterials showed good virucidal efficacy and reduced viral infectivity below the detectable limit of the assay. The amount of infectious virus (shown as Log ₁₀ TCID ₅₀ / ml or%) by comparing the amount of virus in the reaction mixture containing each of the nanomaterials and the negative control (containing virus but not nanomaterials) Reduction was obtained. The positive control (low pH) reduced the infectivity of the virus to below the detectable limit of the assay so that no virus was observed.

FIG. 8 shows the amount of infectious virus (Log ₁₀ TCID ₅₀ / ml) present in the test reaction mixture at the end of the reaction time. FIGS. 9 and 10 show the virucidal efficacy of the test nanomaterial as a percentage (%) decrease in infectious titer and as a decrease in virus titer (Log ₁₀ TCID ₅₀ / ml), respectively. The results of the test reaction and the reduction in the amount of infectious virus by adding test nanomaterial (titer,%, and Log ₁₀ TCID ₅₀ / ml) are shown in Table 5, thereby testing the nanomaterial in the virucidal assay The amount of avian H5N1 influenza NIBRG-14 virus that has been quantified after reacting with is reported.

(Table 5)

  The examined nanomaterials (results are shown in Table 5) have a size variation of 5 nm to 100 nm. Tungsten carbide (R32) has a purity of 99.5%. Tungsten carbide (R36, R37, and R38) was produced with different plasma conditions and cooling rates / processes and particle size distributions.

1 shows nanoscale electron microscopic images of influenza and SARS viruses. Shows a mask to prevent airborne particles and viruses. The gap between the fabrics is larger than 10 μm with the current fabric mask. SEM images of filter cloth used in public buildings such as university academic research buildings, shopping centers, and hospitals. Shown are two plates of an HA assay test using nanomaterial as an antiviral agent. Test results showing the antiviral effect of virus reduction caused by different metal, metal oxide and compound nanoparticles (control is on the left). Including nanoparticles such as nano silver, nano TiO ₂ , nano ZnO, nano Cu, nano Ni, nano TiO ₂ (both Anitase and Rotary crystals), nano ZnO, nano SiO ₂ , and steel, Virus reduction of different metals and metal oxides examined. 1 shows a single fiber coated with a mixture of nano and micro scale particles / compounds for antibacterial testing. The percentage reduction in virus titer for nanocompounds of silicon (IV) nitride, tungsten carbide, titanium carbide, titanium carbonitride is shown. Amount of avian H5N1 influenza NIBRG-14 virus quantified after reacting with test nanomaterials in a virucidal assay (Log ₁₀ TCID ₅₀ / ml). The virus titer after antiviral assay of virus titer (Log ₁₀ TCID50 / ml) for nanocompounds of silicon nitride (IV), tungsten carbide, titanium carbide and titanium carbonitride is shown. Percentage reduction (%) of avian H5N1 influenza NIBRG-14 virus after reacting with test nanomaterial in virucidal assay. Shows log reduction of H5N1 virus for silicon (IV) nitride, tungsten carbide, titanium carbide, titanium carbonitride nanocompounds (results expressed as log titer reduction for nanocompounds). Viral titer reduction of avian H5N1 influenza NIBRG-14 virus after reacting with test nanomaterial in virucidal assay (Log ₁₀ TCID ₅₀ / ml).

Claims (27)

For the cause and / or preventing reduce viral infection, a compound of the general formula M _n X _y, wherein, M is (i) calcium (Ca), aluminum (Al), zinc (Zn), nickel ( A metal selected from the group consisting of Ni), tungsten (W), or copper (Cu);
Or (ii) a non-metal selected from the group consisting of silicon (Si), boron (B), or carbon (C);
n is equal to 1, 2, or 3,
And X is (iii) a non-metal selected from the group consisting of oxygen (O), nitrogen (N), or carbon (C);
Or (iv) phosphate (PO ₄ ³⁻ ), hydrogen phosphate (HPO ₄ ²⁻ ), dihydrogen phosphate (H ₂ PO ₄ ⁻ ), carbonate (CO ₃ ), silicate (SiO ₄ ²⁻ ), sulfate ( An anion selected from the group consisting of SO ₄ ²⁻ ), nitrate (NO ₃ ⁻ ), nitrite (NO ₂ ⁻ );
y equals 0, 1, 2, 3, or 4;
Use of compound nanoparticles.   2. Use according to claim 1, wherein the nanoparticles have an average particle size of up to 100 nm.   The use according to claim 2, wherein the nanoparticles have an average particle size ranging from about 1 nm to about 90 nm. The compounds of the general formula M _n X _y is, oxides, carbonates, silicates, carbides, nitrides, and / or phosphate, the use of any one of claims 1 to 3. Compounds of the general formula M _n X _y are aluminum oxide (Al ₂ O ₃ ), silicon dioxide (SiO ₂ ), zinc oxide (ZnO), aluminum phosphate (AlPO ₄ ), aluminum hydrogen phosphate (A1 ₂ (HPO _{4 3} ), aluminum dihydrogen phosphate (Al (H ₂ PO ₄ ) ₃ ), calcium oxide (CaO), calcium carbonate (CaCO ₃ ), calcium silicate (CaSiO ₄ ), calcium phosphate (Ca ₃ (PO ₄ ) ₂ ), Calcium hydrogen phosphate (CaHPO ₄ ), or calcium dihydrogen phosphate (Ca (H ₂ PO ₄ )), silicon nitride (SiN), silicon carbide (SiC), boron nitride (BN), tungsten carbide (WC) And the use according to claim 4 selected from the group consisting of titanium carbonitride (TiC _0.5 N _0.5 ). Nanoparticles comprise a mixed composition of at least two compounds of the general formula M _n X _y as defined in claim 1. The use of any one of claims 1-5. Mixed composition of nanoparticles, copper (Cu), copper oxide (II) (CuO), and / or copper oxide _{(I) (Cu 2 O)} , Use according to claim 5, wherein. The nanoparticle is a compound of the general formula M _n X _y as defined in claim 1 and aluminum (Al), silicon (Si), zinc (Zn), nickel (Ni), or combinations thereof 6. Use according to any one of claims 1 to 5, comprising a mixed composition with one or more. Nanoparticles
(I) Aluminum (Al) and aluminum oxide (Al ₂ O ₃ ),
(Ii) silicon (Si) and silicon dioxide (SiO ₂ ),
(Iii) silicon (Si) and silicon carbide (SiC),
(Iv) zinc (Zn) and zinc oxide (ZnO), or (v) nickel (Ni) and nickel (II) oxide (NiO)
9. Use according to claim 8, comprising or a combination thereof. Nanoparticles further comprises a titanium dioxide (TiO _2), the use of any one of claims 1 to 5. Nanoparticles, further comprises zinc oxide (ZnO) and titanium dioxide (TiO _2), the use of claim 10, wherein.   Nanoparticles are boron (B), carbon (C), aluminum (Al), silicon (Si), phosphorus (P), calcium (Ca), titanium (Ti), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), silver (Ag), zinc (Zn), copper (Cu), sulfur (S), nickel (Ni), gold (Au), zirconium (Zr), ytterbium (Yb), zirconium The use of nanoparticles according to any one of claims 1 to 5, further comprising an element selected from the group consisting of (Zr) or an oxide thereof or a combination thereof. Use according to claim 12, wherein the nanoparticles further comprise at least one of the following combinations of elements:
CP-Ag-Zn, CP-Cu-S, CP-Cu-Ni-S, C-Si-Ag-Zn, C-Si-Cu-S, C-Si-Cu-Ni, C-Cu-Zn- W, C-Cu-Zn-Ag, C-Cu-Zn-W-Ag, CW-Ti-B, CW-Ti-N, C-Ti-N, Si-N, Ti-N, Al-N, BN, Al-B. 6. Use according to any one of claims 1 to 5, wherein the nanoparticles further comprise at least one of the following oxides:
_{TiO 2, Cu 2 O, CuO} , ZnO, NiO, Al 2 O 3, FeO, Fe 2 O 3, Fe 3 O 4, CoO, Co 3 O 4, or Si ₂ O _3, or combinations thereof. Use of mixed nanoparticles of zinc oxide (ZnO) and titanium dioxide (TiO ₂ ) to reduce and / or prevent viral transmission.   The virus consists of influenza, measles, coronavirus, mumps, marburg, ebola, rubella, rhinovirus, poliovirus, hepatitis A, smallpox, varicella, SARS, HIV, rotavirus, norwalk virus, and adenovirus 16. Use according to any one of claims 1 to 15, selected from the group. A compound of the general formula M _n X _y , wherein M is from (i) calcium (Ca), aluminum (Al), zinc (Zn), nickel (Ni), tungsten (W) or copper (Cu) A metal selected from the group consisting of:
Or (ii) a non-metal selected from the group consisting of silicon (Si), boron (B), or carbon (C);
n is equal to 1, 2, or 3,
And X is (iii) a non-metal selected from the group consisting of oxygen (O), nitrogen (N), or carbon (C);
Or (iv) phosphate (PO ₄ ³⁻ ), hydrogen phosphate (HPO ₄ ²⁻ ), dihydrogen phosphate (H ₂ PO ₄ ⁻ ), carbonate (CO ₃ ), silicate (SiO ₄ ²⁻ ), sulfate ( An anion selected from the group consisting of SO ₄ ²⁻ ), nitrate (NO ₃ ⁻ ), nitrite (NO ₂ ⁻ );
y equals 0, 1, 2, 3, or 4;
A method for the reduction and / or prevention of viral transmission comprising the step of applying a nanoparticulate composition of a compound to a protective clothing article. A compound of the general formula M _n X _y , wherein M is from (i) calcium (Ca), aluminum (Al), zinc (Zn), nickel (Ni), tungsten (W) or copper (Cu) A metal selected from the group consisting of:
Or (ii) a non-metal selected from the group consisting of silicon (Si), boron (B), or carbon (C);
n is equal to 1, 2, or 3,
And X is (iii) a non-metal selected from the group consisting of oxygen (O), nitrogen (N), or carbon (C);
Or (iv) phosphate (PO ₄ ³⁻ ), hydrogen phosphate (HPO ₄ ²⁻ ), dihydrogen phosphate (H ₂ PO ₄ ⁻ ), carbonate (CO ₃ ), silicate (SiO ₄ ²⁻ ), sulfate ( An anion selected from the group consisting of SO ₄ ²⁻ ), nitrate (NO ₃ ⁻ ), nitrite (NO ₂ ⁻ );
y equals 0, 1, 2, 3, or 4;
A method for reducing and / or preventing viral transmission comprising applying a composition of compound nanoparticles to a filter. A compound of the general formula M _n X _y , wherein M is from (i) calcium (Ca), aluminum (Al), zinc (Zn), nickel (Ni), tungsten (W) or copper (Cu) A metal selected from the group consisting of:
Or (ii) a non-metal selected from the group consisting of silicon (Si), boron (B), or carbon (C);
n is equal to 1, 2, or 3,
And X is (iii) a non-metal selected from the group consisting of oxygen (O), nitrogen (N), or carbon (C);
Or (iv) phosphate (PO ₄ ³⁻ ), hydrogen phosphate (HPO ₄ ²⁻ ), dihydrogen phosphate (H ₂ PO ₄ ⁻ ), carbonate (CO ₃ ), silicate (SiO ₄ ²⁻ ), sulfate ( An anion selected from the group consisting of SO ₄ ²⁻ ), nitrate (NO ₃ ⁻ ), nitrite (NO ₂ ⁻ );
y equals 0, 1, 2, 3, or 4;
A protective clothing article composed of fibers coated with a composition of compound nanoparticles.   20. The protective clothing article according to claim 19, wherein the protective clothing article is made of natural fiber.   20. The protective clothing article according to claim 19, wherein the protective article is made of artificial fiber.   The protective clothing article according to any one of claims 19, 20, or 21, which is a face mask.   The garment according to any one of claims 19, 20, or 21, selected from the group consisting of a face mask, a surgical mask, a respirator mask, a hat, a hood, trousers, a shirt, gloves, a skirt, a boiler suit, and a surgical gown. Supplies. A compound of the general formula M _n X _y , wherein M is from (i) calcium (Ca), aluminum (Al), zinc (Zn), nickel (Ni), tungsten (W) or copper (Cu) A metal selected from the group consisting of:
Or (ii) a non-metal selected from the group consisting of silicon (Si), boron (B), or carbon (C);
n is equal to 1, 2, or 3,
And X is (iii) a non-metal selected from the group consisting of oxygen (O), nitrogen (N), or carbon (C);
Or (iv) phosphate (PO ₄ ³⁻ ), hydrogen phosphate (HPO ₄ ²⁻ ), dihydrogen phosphate (H ₂ PO ₄ ⁻ ), carbonate (CO ₃ ), silicate (SiO ₄ ²⁻ ), sulfate ( An anion selected from the group consisting of SO ₄ ²⁻ ), nitrate (NO ₃ ⁻ ), nitrite (NO ₂ ⁻ );
y equals 0, 1, 2, 3, or 4;
A filter composed of fibers coated with a composition of compound nanoparticles.   25. The filter according to claim 24, wherein the filter is composed of natural fibers.   25. The filter according to claim 24, comprising an artificial fiber.   27. A filter according to any one of claims 24, 25 or 26, which is an air filter.

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